This present invention relates generally to electronic systems for carrying out nucleic acid sequencing.
Arrays are often used in the fields of molecular biology, biochemistry and other life sciences for analyzing biological molecules, including nucleic acids (DNA, RNA) and proteins (enzymes, antigens, etc.) that have been tagged or labeled for detection. Many different surface preparation methods exist for the creation of such arrays, although the majority of techniques currently in use for array construction are primarily chemical in nature. Photolithographic techniques are widely used in the many conventional technologies to pattern arrays of biological features (e.g., nucleic acids such as DNA or RNA) onto substantially planar surfaces.
For example, a biological array can be obtained by providing an array substrate that is chemically treated, for example with hexamethyldisilazane (HMDS), which is known to have a low affinity for biological molecules such as nucleic acids, coated with a photoresist layer, and by etching the surface to provide discrete areas with exposed HMDS. The surface can then be further modified to produce array features composed of an aminosilane such as aminopropyldimethylethoxysilane (APDMES), which gives rise to active amino groups at the surface. In aqueous solution, the amino group features of the APDMES protonate to form a positively charged surface which, through electrostatic charges, will attract any biological molecules such as DNA and RNA, which have negatively-charged phosphate backbones.
Such previously described arrays are created by processes that are chemical in nature and electronically passive, and thus they have a number of limitations. First, the loading of biological samples to the array is limited in efficiency, as the substrates are generally exposed to air and thus exposed to contaminants prior to the loading of the biological molecules. In addition, the attractive forces of the binding of the biological molecules to the surface cannot be varied, since the forces are limited to the fixed, initial amine density on the surface. Thus, the topological distribution of the molecules is fixed, and neither the position nor the relative size of the biological molecules can be varied following array construction.